This application requests a 5-year renewal of the Center for Environmental Genetics (CEG). The unifying research focus of the Center is to study the impact of genetic diversity on individual susceptibility to deleterious environmental agents. The CEG has a long 15-year history of accomplishments in environmental genetics that helps shape one of the nation's current top priorities in environmental health sciences (EHS) research. The investigators will expand their pioneering efforts and propose the following aims for the next funding period. Aim 1: To promote research in gene-environment interactions in human health and disease by emphasizing the use of environmental exposures in relationship with genetic variations and epigenetic reprogramming to inform pathophysiologic endpoints. Aim 2: To hasten translation of basic biomedical EHS research and population-based studies into clinical practices for disease prevention, diagnosis, and prognosis. Reciprocally, Center activities will afford opportunities for novel hypotheses to be generated from human based studies to be tested in laboratory settings. Aim 3: To foster the development of sensitive pathophysiological markers for the assessment of internal dose and improve measures of body burden;to undertake the discovery predictive makers so that the effects of early life exposure on later-life disease risk could be anticipated and minimized through innovative intervention measures. Validation of these markers through quantitative and qualitative measurements of phenotype or clinical outcomes will be an integral part of this aim. Aim 4: To attract and train the next generation of biomedical EHS investigators and clinicians with a strong desire to apply EHS in their clinical practices through partnership of the investigators'comprehensive Career Development Program (CDP) and a newly established Master Degree in Clinical Training program. A Pilot Project Program will function to continue support young investigators till they attain independence in EHS research, and to recruit new-to-EHS scientists. Three Facility/Service Cores will facilitate attainment of the goals: 1) the Integrative Technology Services Core will inject leading edge technologies into EHS research;2) the Integrative Health Services Core will help manage and share epidemiological and clinical databases, support tissue procurement, and development of clinical protocols;and 3) the Informatics Core will support all levels of data-mining and hypothesis-creation opportunities from various systems biology and clinical investigations. The overarching objective of the Center is to improve human health through effective integration of basic, clinical and epidemiological research, germane to gene-environment interaction, toward the ultimate goal of delivering "personalized" medicine and devising public health initiatives for susceptible populations. The multiplicity of expertise and strong fund holding amongst membership, and the unyielding commitment from institution leadership constitute the elements of success in this application.